Vascular Medicine Institute, Department of Medicine, University of Pittsburgh, BST E1259, 200 Lothrop Street, Pittsburgh, PA, 15261, USA.
Center for Metabolism and Mitochondrial Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Sci Rep. 2023 Apr 15;13(1):6134. doi: 10.1038/s41598-023-33308-7.
G-protein coupled receptors (GPCRs) mediate signal transduction from the cellular surface to intracellular metabolic pathways. While the function of many GPCRs has been delineated previously, a significant number require further characterization to elucidate their cellular function. G-protein coupled receptor 19 (GPR19) is a poorly characterized class A GPCR which has been implicated in the regulation of circadian rhythm, tumor metastasis, and mitochondrial homeostasis. In this report, we use a novel knockout (KO) mouse model to examine the role of GPR19 in whole-body metabolic regulation. We show that loss of GPR19 promotes increased energy expenditure and decreased activity in both male and female mice. However, only male GPR19 KO mice display glucose intolerance in response to a high fat diet. Loss of GPR19 expression in male mice, but not female mice, resulted in diet-induced hepatomegaly, which was associated with decreased expression of key fatty acid oxidation genes in male GPR19 KO livers. Overall, our data suggest that loss of GPR19 impacts whole-body energy metabolism in diet-induced obese mice in a sex-dependent manner.
G 蛋白偶联受体 (GPCRs) 将细胞表面的信号转导到细胞内代谢途径。虽然许多 GPCR 的功能以前已经被描述过，但仍有相当数量的 GPCR 需要进一步表征，以阐明其细胞功能。G 蛋白偶联受体 19（GPR19）是一种特征尚不明确的 A 类 GPCR，它与昼夜节律的调节、肿瘤转移和线粒体稳态有关。在本报告中，我们使用一种新型的敲除（KO）小鼠模型来研究 GPR19 在全身代谢调节中的作用。我们发现，GPR19 的缺失会促进雄性和雌性小鼠的能量消耗增加和活动减少。然而，只有雄性 GPR19 KO 小鼠在高脂肪饮食后表现出葡萄糖不耐受。在雄性小鼠中缺失 GPR19 的表达，而不是在雌性小鼠中，导致饮食诱导的肝肿大，这与雄性 GPR19 KO 肝脏中关键脂肪酸氧化基因的表达减少有关。总的来说，我们的数据表明，GPR19 的缺失以性别依赖的方式影响肥胖诱导的小鼠的全身能量代谢。
